Jointly use sWGS and WES data

[WangKang-Leo]

Dear

I read this great publication (https://www.nature.com/articles/s41586-021-04278-5) from Caldas group. They presented a very reasonable input for our translational studies (shallow whole-genome sequence and whole-exome sequence), jointly use log ratios from sWGS (LogR data) and germline SNP data (BAF data) from WES.

I am just confused given BAF and logR data have the same number of the rows as input for ASCAT, sWGS won't provide extra values here, because only those bins on the exome are used.......why don't use copy ratio data derived from WES. Or I am misunderstanding here, we can input copy ratios in whole-genome wide (sWGS) and SNP information on exome (WES).

I followed the tutorial of sarek3.2.1 (https://nf-co.re/sarek/3.2.1/usage#how-to-run-ascat-with-whole-exome-sequencing-data) that wrapped ASCAT, but get bad purity distribution based on WES data....

Thanks in advance
Kang

[tlesluyes]

Hi @WangKang-Leo,

Not sure I understand your question, it sounds related to some methods section in a study where we haven't participated so I suggest you contact the authors and ask for some clarification.

I've never heard of sarek and I recommend running ASCAT rather than a wrapper that might make the process of getting CNA profiles more complicated and/or confusing. All of the methods and reference files are described in this GitHub repo, it shouldn't be hard to derive profiles from HTS data (but let me know if it is and I'll update the doc to make it clearer).

Cheers,

Tom.